Paper
13 July 2009 The correlation between photosensitizers' membrane localization, membrane-residing targets, and photosensitization efficiency
Shany Ytzhak, Shoshana Bernstein, Leslie M. Loew, Benjamin Ehrenberg
Author Affiliations +
Proceedings Volume 7380, Photodynamic Therapy: Back to the Future; 738029 (2009) https://doi.org/10.1117/12.827045
Event: 12th World Congress of the International Photodynamic Association, 2009, Seattle, Washington, United States
Abstract
Various tetrapyrroles act as photosensitizers by efficiently generating singlet oxygen. Hydrophobic or amphiphilic photosensitizers are taken up by cells and are usually located in various cellular lipid membranes. Passive uptake by a membrane depends on biophysical properties of the membrane, such as its composition, temperature, phase, fluidity, electric potential etc., as well as on the external solution's properties. Although the intrinsic lifetime of singlet oxygen in the membrane phase is 10-30 μs, depending on lipid composition, it escapes much faster out of the membrane into the external or internal aqueous medium, where its lifetime is <3 μs. Any damage that singlet oxygen might inflict to membrane constituents, i.e. proteins or lipids, must thus occur while it is diffusing in the membrane. As a result, photosensitization efficiency depends, among others, on the location of the sensitizer in the membrane. Singlet oxygen can cause oxidative damage to two classes of targets in the membrane: lipids and proteins. Depolarization of the Nernst electric potential on cells' membranes was observed, but it is not clear whether lipid oxidation is a relevant factor leading to abolishing the resting potential of cells' membranes and to their death. We present a study of the effect of membrane lipid composition and the dissipation of the electric potential that is generated across the membrane. We find a clear correlation between the structure and unsaturation of lipids and the leakage of the membrane, which can be caused by their photosensitized oxidization. We demonstrate here that when liposomes are composed of mixtures similar to natural membranes, and photosensitization is being carried out under usual PDT conditions, photodamage to the lipids is not likely to cause enhanced permeability of ions through the membrane, which could be a mechanism that leads to cell death.
© (2009) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Shany Ytzhak, Shoshana Bernstein, Leslie M. Loew, and Benjamin Ehrenberg "The correlation between photosensitizers' membrane localization, membrane-residing targets, and photosensitization efficiency", Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 738029 (13 July 2009); https://doi.org/10.1117/12.827045
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Cited by 3 scholarly publications.
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KEYWORDS
Luminescence

Ions

Oxygen

Photodynamic therapy

Cell death

Diffusion

Photosensitizer targeting

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